Sensitive detection of extremely small iron oxide nanoparticles in living mice using MP2RAGE with advanced image co-registration

Joong H Kim; Stephen Dodd; Frank Q Ye; Andrew K Knutsen; Duong Nguyen; Haitao Wu; Shiran Su; Simone Mastrogiacomo; Thomas J Esparza; Rolf E Swenson; David L Brody

doi:10.1038/s41598-020-80181-9

Sensitive detection of extremely small iron oxide nanoparticles in living mice using MP2RAGE with advanced image co-registration

Sci Rep. 2021 Jan 8;11(1):106. doi: 10.1038/s41598-020-80181-9.

Authors

Joong H Kim^{1

2}, Stephen Dodd², Frank Q Ye³, Andrew K Knutsen¹, Duong Nguyen², Haitao Wu⁴, Shiran Su^{2

5}, Simone Mastrogiacomo², Thomas J Esparza^{1

2}, Rolf E Swenson⁴, David L Brody^{6

7

8}

Affiliations

¹ Center for Neuroscience and Regenerative Medicine, Henry M. Jackson Foundation, Bethesda, MD, USA.
² Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
³ Neurophysiology Imaging Facility, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, and National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
⁴ Chemistry and Synthesis Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
⁵ Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.
⁶ Center for Neuroscience and Regenerative Medicine, Henry M. Jackson Foundation, Bethesda, MD, USA. david.brody@usuhs.edu.
⁷ Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. david.brody@usuhs.edu.
⁸ Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. david.brody@usuhs.edu.

Abstract

Magnetic resonance imaging (MRI) is a widely used non-invasive methodology for both preclinical and clinical studies. However, MRI lacks molecular specificity. Molecular contrast agents for MRI would be highly beneficial for detecting specific pathological lesions and quantitatively evaluating therapeutic efficacy in vivo. In this study, an optimized Magnetization Prepared-RApid Gradient Echo (MP-RAGE) with 2 inversion times called MP2RAGE combined with advanced image co-registration is presented as an effective non-invasive methodology to quantitatively detect T1 MR contrast agents. The optimized MP2RAGE produced high quality in vivo mouse brain T1 (or R1 = 1/T1) map with high spatial resolution, 160 × 160 × 160 µm³ voxel at 9.4 T. Test-retest signal to noise was > 20 for most voxels. Extremely small iron oxide nanoparticles (ESIONPs) having 3 nm core size and 11 nm hydrodynamic radius after polyethylene glycol (PEG) coating were intracranially injected into mouse brain and detected as a proof-of-concept. Two independent MP2RAGE MR scans were performed pre- and post-injection of ESIONPs followed by advanced image co-registration. The comparison of two T1 (or R1) maps after image co-registration provided precise and quantitative assessment of the effects of the injected ESIONPs at each voxel. The proposed MR protocol has potential for future use in the detection of T1 molecular contrast agents.

Publication types

Evaluation Study
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / diagnostic imaging*
Contrast Media / chemistry*
Female
Magnetic Iron Oxide Nanoparticles / chemistry*
Magnetic Resonance Imaging / instrumentation
Magnetic Resonance Imaging / methods*
Mice
Mice, Inbred C57BL
Sensitivity and Specificity

Substances

Contrast Media